It is already known that the barrier function of the skin can be attenuated by employing a penetration enhancer such as dimethylsulphoxide (DMSO), N-methyl-pyrrolidone, dimethylformamide (DMF), oleic acid or N-dodecylazacycloheptanone-2.
However, penetration enhancers may exert their action through interactions with the lipid bilayers within the intercellular spaces of the stratum corneum. Penetration enhancers such as N-dodecylazacycloheptanone-2 and oleic acid disrupt lipid organization and increase lipid fluidity [Golden G. M., Mckie J. E. and Potts R. O., J. Pharm. Sci. 76: 25-28, 1987].
Penetration enhancers may therefore have systemic toxicity or induce local irritation or alterations to the skin. The use of penetration enhancers is described in detail by Barry B. W. in "Percutaneous Absorption", Chapters 31 and 33, pages 531 to 554 and 567 to 593 [Bronaugh R. L. and Maibach H. I., eds. Dekker (New York) 1989] and by Walters K. A. in "Transdermal Drug Delivery--Developmental issues and Research Initiatives", pages 197-246 [Hadgraft J. and Guy R. H., eds., Dekker (New York) 1989].
Iontophoresis has also been known for a long time to enhance the penetration of active substances into the skin.
According to this technique, an electric current is applied to skin at the same time as the active substance.
Iontophoresis may be defined as the use of electrorepulsive and/or electro-osmotic forces to facilitate the transport of a species across the skin. The former force is employed when a charged molecule is repelled across the skin.
The principle of employing an electro-osmotic force is to enable certain non-charged molecules to be pulled along in the electrically induced solvent flow. In this technique, the current is maintained for a prolonged period. The current may be continuous or pulsed.
However, iontophoresis has certain disadvantages. The drug substances may be unstable in the presence of an electric field and moreover, the long duration of application of the electric current may be uncomfortable or traumatizing for the patient.